Chronic obstructive pulmonary disease (COPD) currently lacks effective treatments to halt disease progression, making the search for preventive and therapeutic drugs a pressing issue. Natural products, with their accessibility, affordability, and low toxicity, offer promising avenues. Investigating the pharmacological effects and related signaling mechanisms of active components from natural products on COPD animal models induced by various triggers has become an important focus. In animal models induced by cigarette smoke, cigarette smoke combined with lipopolysaccharide (LPS), air pollution, elastase, bacterial or viral infections, the active compounds of natural products, such as flavonoids, terpenoids, and phenolics, can exert anti-inflammatory, antioxidant, mucus-regulating, and airway remodeling-inhibiting effects through key signaling pathways including nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB), and mitogen-activated protein kinase (MAPK). These findings not only provide a theoretical basis for the clinical diagnosis and treatment of COPD but also point to new directions for future scientific research.
Pulmonary Disease, Chronic Obstructive/etiology* ; Animals ; Disease Models, Animal ; Biological Products/pharmacology* ; Humans ; NF-kappa B/metabolism* ; Flavonoids/pharmacology* ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Heme Oxygenase-1/metabolism* ; Terpenes/pharmacology* ; Antioxidants/pharmacology* ; NF-E2-Related Factor 2/metabolism* ; Smoke/adverse effects* ; Phenols/therapeutic use*

Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp domain. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.
Nipah Virus/chemistry* ; Cryoelectron Microscopy ; Viral Proteins/genetics* ; RNA-Dependent RNA Polymerase/genetics* ; Phosphoproteins/genetics* ; Humans ; Models, Molecular ; Protein Binding

Objective:To summarise the clinical application and results of superficial peroneal artery perforator flaps in tiled reconstruction of thumbs and fingers.Methods:From June 2020 to June 2022, 8 patients with finger or thumb defects (4 thumbs, 2 index fingers and 2 middle fingers) received digit reconstruction in the Department of Hand Surgery, Suzhou Ruihua Orthopaedic Hospital. Two thumbs (2 patients) were reconstructed with a free partial hallux nail flap combined with a free perforator flap of superficial peroneal artery and an iliac bone graft, 1 thumb was reconstructed with a free partial hallux nail flap combined with a free perforator flap of superficial peroneal artery, 1 thumb and 2 middle fingers were reconstructed with free perforator flaps of superficial peroneal artery combined with iliac bone grafts, and 2 index fingers were reconstructed with lobulated free perforator flaps of superficial peroneal artery. The sizes of the flaps were 1.8 cm×3.2 cm-4.0 cm×10.0 cm. Lengths of iliac crest were 1.5-4.0 cm. The donor sites were directly sutured in 5 patients, skin grafts in 2 and superficial peroneal artery perforator flap reconstruction in 1 patient. Postoperative observations included survival of the digits and healing of the bone grafts. Monthly scheduled postoperative follow-ups were conducted at outpatient clinics and via telephone or WeChat reviews, covering function and appearance of the reconstructed digits, impact on the function and appearance of donor sites as well as the satisfaction of patients.Results:All 8 reconstructed digits survived in one stage and all the 5 bone grafts healed at 3 to 4 months after surgery. The mean postoperative follow-up period was 10 months, ranged 4 to 20 months. The texture of the reconstructed digits was close to that of the recipient site and good in elasticity, without purplish while in cold, nor ulceration, obvious bloating and pigmentation. Sensation of the digit pulps was recovered to S 2 to S 3, and the sensation in touch, pain and temperature were restored. TPD was not checked. There was no noticeable hyperplasia nor pain in the recipient and donor sites. There was no obvious hyperplasia or pain at the donor sites for the hallux nail flap, and the skin grafts or flaps in the donor sites survived well without ulceration or pain and the function of the donor feet were not affected. Functions of the reconstructed digits were assessed according to the Functional Assessment Criteria for Thumb and Finger Reconstruction of the Society for Evaluation Standard of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, 4 patients achieved in excellent and 4 in good. According to the University of Michigan Hand Profile Questionnaire (MHQ), patient satisfaction was found very satisfied with 4 patients and satisfied with the other 4 patients. Conclusion:The superficial peroneal artery perforator flap has advantages of thin and large area with pleasant texture, better sensation recovery and less damage to the donor site. It is an ideal flap for reconstruction of thumbs and fingers.

Patients with hepatocellular carcinoma (HCC) and bone metastasis (BM) suffer from greatly reduced life quality and a dismal prognosis. However, BM in HCC has long been overlooked possibly due to its relatively low prevalence in previous decades. To date, no consensus or guidelines have been reached or formulated for the prevention and management of HCC BM. Our narrative review manifests the increasing incidence of HCC BM to sound the alarm for additional attention. The risk factors, diagnosis, prognosis, and therapeutic approaches of HCC BM are detailed to provide a panoramic view of this disease to clinicians and specialists. We further delineate an informative cancer bone metastatic cascade based on evidence from recent studies and point out the main factors responsible for the tumor-associated disruption of bone homeostasis and the formation of skeletal cancer lesions. We also present the advances in the pathological and molecular mechanisms of HCC BM to shed light on translational opportunities. Dilemmas and challenges in the treatment and investigation of HCC BM are outlined and discussed to encourage further endeavors in the exploration of underlying pathogenic and molecular mechanisms, as well as the development of novel effective therapies for HCC patients with BM.
Bone Neoplasms/secondary* ; Carcinoma, Hepatocellular/therapy* ; Humans ; Liver Neoplasms/therapy* ; Prognosis

Objective:To explore the effect of mobile health management model in patients with acute myocardial infarction after percutaneous coronary intervention (PCI) under the background of "Internet +".Methods:From July 2018 to March 2020, convenience sampling was used to select 124 patients with acute myocardial infarction who underwent PCI successfully in the First Affiliated Hospital of Zhengzhou University as the research object. According to the random number table method, the patients were divided into the observation group and the control group, 62 cases in each group. The control group received routine nursing after surgery, and the observation group was given the mobile health management model under the background of "Internet +" on the basis of the control group. Self-management Scale for Patients Undergone Coronary Artery Stent Implantation, Hamilton Depression Scale (HAMD) , Hamilton Anxiety Scale (HAMA) , and Nursing Satisfaction Questionnaire were used to evaluate the effect of the intervention.Results:After six months of intervention, the scores of each dimension of the Self-management Scale for Patients Undergone Coronary Artery Stent Implantation in the observation group were higher than those in the control group, and the differences were statistically significant ( P<0.05) . After six months of intervention, the HAMD and HAMA scores of the observation group were lower than those of the control group, and the differences were statistically significant ( P<0.05) . After six months of intervention, the nursing satisfaction of the observation group was higher than that of the control group, and the difference was statistically significant ( P<0.05) . Conclusions:The mobile health management model under the background of "Internet +" is conducive to improving the self-management ability of patients with acute myocardial infarction after PCI, reducing patients' depression and anxiety, and increasing patients' satisfaction with nursing.

Objective:To investigate the predictive value of cerebroplacental ratio (CPR) for adverse perinatal outcomes of induction of labor in prolonged pregnancy.Methods:This retrospective study recruited 315 singleton pregnant women who had induced labor due to prolonged pregnancy (≥41 gestational weeks) in the First Affiliated Hospital of Chongqing Medical University from January 1, 2019 to April 30, 2020. Based on the occurrence of adverse perinatal outcomes (emergency delivery due to persistent abnormal fetal heart rate monitoring, umbilical artery blood pH at birth <7.2, 5 min Apgar scores<7, transferring to neonatal intensive care unit after birth, chorioamnionitis and vaginal delivery converted to cesarean section), they were divided into two groups: case group ( n=76) and normal group ( n=239). Clinical features and umbilical artery blood flow, middle cerebral artery (MCA) flow and CPR measured in the last ultrasound scan before induction were compared between the two groups using student's t-test, Mann-Whitney U test and Chi-square test. Receiver operating characteristic (ROC) curve was used to analyze the predictive values of umbilical artery blood flow, MCA flow and CPR for the adverse perinatal outcomes. Multivariate logistic regression analysis was used to screen the meaningful predictors. Results:Compared with the normal group, the umbilical artery pulsatility index (PI) (0.9±0.1 vs 0.8±0.1, t=-5.458, P<0.001) and the percentage of abnormal CPR (<1.0) increased significantly [21.1%(16/76) vs 6.3%(15/239), χ2=14.190, P<0.001] in the case group, while the MCA-PI and CPR decreased significantly (1.1±0.2 vs 1.3±0.3, t=5.658, P<0.001; 1.2±0.3 vs 1.6±0.5, t=8.940, P<0.001). The areas under the ROC curves of umbilical artery PI, MCA-PI and CPR for predicting adverse perinatal outcomes were 0.71, 0.71 and 0.77, respectively. CPR had the highest sensitivity (0.74) compared with umbilical artery PI (0.68) and MCA-PI (0.71), but the specificity of them were similar (0.67, 0.66 and 0.66). Multivariate logistic regression analysis showed that only CPR was the independent risk factor for adverse perinatal outcomes ( OR=0.028, 95% CI: 0.010-0.080, P<0.001). Conclusions:As an indicator for early prediction of adverse perinatal outcomes of induction of labor in prolonged pregnancy, CPR was more sensitive but less specific.

Objective:To explore the correlation between early exercise capacity, mental state and quality of life in patients with acute myocardial infarction after percutaneous coronary intervention (PCI) .Methods:Using the convenient sampling method, a total of 120 patients with acute myocardial infarction treated by PCI who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2020 to January 2021 as the research objects. Exercise cardiopulmonary test system, Positive and Negative Emotion scale and SF-36 were used to investigate.Results:In 120 patients with acute myocardial infarction, oxygen uptake at anaerobic threshold after PCI was (8.11±0.95) ml/ (kg·min) , peak metabolic capacity was (3.04±0.12) METs, peak oxygen uptake was (10.97±1.25) ml/ (kg·min) and the metabolic equivalent at the anaerobic threshold was (2.25±0.12) METs. The early exercise capacity of patients with acute myocardial infarction after PCI was positively correlated with positive emotions and quality of life ( P<0.01) , and negatively correlated with negative emotions ( P<0.01) . Conclusions:There is a positive correlation between early exercise ability and positive emotions and quality of life in patients with acute myocardial infarction after PCI.

Objective:To explore the feasibility of high-flow nasal cannula(HFNC)therapy for respiratory failure in elderly patients.Methods:A total of 300 patients with respiratory failure admitted to Peking University Shougang Hospital from December 2016 to March 2019 were enrolled in this prospective study.Patients were divided into three groups: the HFNC group, the conventional oxygen therapy(COT)group and the non-invasive positive pressure ventilation(NPPV)group(n=100 in each group). Arterial oxygen saturation(SPO 2), oxygen index(OI), heart rate(HR), respiratory rate(RR), mean arterial pressure(MAP), comfort level, discharge rate, tracheal intubation rate, rate of referral to ICU, mortality and rate of referral to another group after therapy were compared between the HFNC and COT groups and between the HFNC and NPPV groups. Results:SPO 2 after oxygen therapy for 30 minutes( t=-2.992, P=0.003), 1 hour( t=-2.884, P=0.005)and 6 hours( t=-3.196, P=0.002)and OI before discharge( t=-2.060, P=0.048)were higher in the HFNC group than in the COT group.The HR in the above two groups was lower before discharge than before therapy, and the HR in the COT group was even lower(73.1±25.1 beat per minute vs.75.1±25.9 beat per minute), but both were within the normal range.The discharge rate was higher( χ2=-1.969, P=0.049), while the rate of referral to another group was lower in the HFNC group than in the COT group( χ2=-3.115, P=0.002). There was no significant difference in the tracheal intubation rate, ICU transfer rate and mortality between the HFNC and COT groups.SPO 2 after oxygen therapy for 30 minutes( t=-2.026, P=0.046)and 6 hours( t=-2.101, P=0.040)were higher in the HFNC group than in the NPPV group, but there was no significant difference in OI and SPO 2 between the two groups before discharge.The HR in both HFNC and NPPV groups was lower before discharge than before therapy, and there was no statistical difference between the two groups.The mortality, discharge rate, tracheal intubation rate, ICU transfer rate and rate of referral to another group had no significant difference between the HFNC and NPPV groups.The comfort level was higher in the HFNC group than in the COT and NPPV groups( t=-3.758 and -19.180, both P=0.000). Conclusions:HFNC is a new type of oxygen therapy equipment introduced after COT and NPPV, and possesses more advantages for elderly patients with respiratory failure.

Objective To investigate clinical significance of combined detection of serum C 3bR and IL-6 in patients with traumatic brain injury.Methods 48 patients with TBI admitted in 371 Central Hospital of PLA from May 2016 to May 2017 were randomly selected as the subjects,including 26 males and 22 females,aged 25 to 60 years,with an average age of(43.7 ± 5.8)years.Admission according to the injury by Glasgow coma score(GCS):≤7 points in 18 cases,≥8 points in 30 cases.Another 30 healthy people who were admitted to the hospital for the same period were selected as the control group.Serum C3bR and IL-6 levels were meas-ured by ELISA in the study group at 1,3 and 7 days after admission,and the expression of C3bR and IL-6 were analyzed.Results The level of serum C3bR in the first and the third day after traumatic brain injury was significantly lower than that in the control group,and the level of IL-6 after craniocerebral injury was signifi-cantly higher than that of the control group(P<0.05).In the observation group,the level of C3bR was signif-icantly higher than that of ≤ 7,and the level of IL-6 was significantly lower than that of the severe GCS score ≥8(P<0.05).In this study,the serum C3bR,IL-6 and the two joint tests were 0.624,0.641 and 0. 900,respectively area.Conclusion Serum C3bR and IL-6 combined detection can significantly improve the sensitivity of traumatic brain injury diagnosis,so as to understand the severity of traumatic brain injury,w hich could help to assess the disease and determine the prognosis,and have important clinical value.

AIM: To investigate the apoptosis and molecular mechanism of human hepatocellular carcinoma HepG2 cells induced by ginsenoside Rh4.METHODS: Human hepatocellular carcinoma HepG2 cells were treated with ginsenoside Rh4 at doses of 10, 20 and 40 μmol/L, and the inhibitory effect of ginsenoside Rh4 on HepG2 cell viability was measured by MTT assay.The apoptotic rate of HepG2 cells was analyzed by flow cytometry.The morphological changes of the HepG2 cells were observed by Hoechst 33258 and TUNEL staining.The expression of apoptosis-related proteins Bax, Bcl-2, caspase-3 and caspase-9 was determined by Western blot.RESULTS: Ginsenoside Rh4 promoted apoptosis of HepG2 cells in a dose-dependent manner.TUNEL and Hoechst 33258 staining showed that the cells appeared obvious shrinking, swelling and rupture after treated with ginsenoside Rh4 for 24 h.The results of Western blot showed that with the increasing concentrations of ginsenoside Rh4, the expression of pro-apoptotic proteins Bax, cleaved caspase-3 and caspase-9 increased, while anti-apoptotic protein Bcl-2 decreased gradually.CONCLUSION: Ginsenoside Rh4 induces apoptosis of human hepatocellular carcinoma HepG2 cells, and the main mechanism may be related to down-regulation of Bcl-2 and up-regulation of Bax, cleaved caspase-3, and caspase-9.